1-Methylpiperazine → 5-[6-(4-Methyl-piperazine-1-carbonyl)-pyrimidin-4-yloxy]-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 2264613Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2264613
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:38])([F:37])[C:9]1[CH:10]=[C:11]([NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][C:28]4[N:33]=[CH:32][N:31]=[C:30]([C:34]([OH:36])=O)[CH:29]=4)=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)=[O:17])[CH:12]=[CH:13][CH:14]=1.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl.CN(C=O)C.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[F:38][C:8]([F:37])([F:7])[C:9]1[CH:10]=[C:11]([NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][C:28]4[CH:29]=[C:30]([C:34]([N:43]5[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]5)=[O:36])[N:31]=[CH:32][N:33]=4)=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)=[O:17])[CH:12]=[CH:13][CH:14]=1

Komponenten

8

Edukt 3

HCID 531671-MethylpiperazineHCID 65578Oxalyl chlorideHCID 59596375HCID 59596375, Verbindung

Produkt 1

HCID 595963765-[6-(4-Methyl-piperazine-1-carbonyl)-pyrimidin-4-yloxy]-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Versuchsvorschrift

60 μl (0.7 mMol) oxalylchloride are added to a solution of 200 mg (0.45 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid in 4 ml CH2Cl2 and 1 drop of DMF. After 1 h at rt, the solution is concentrated in vacuo. The residue is re-dissolved in THF and 108 μl (0.97 mMol) 1-methylpiperazine are added dropwise. After 2 h stirring, the mixture is diluted with EtOAc and sat. Na2CO3, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; EtOAc→EtOAc/EtOH+2% Et3N 4:1) and crystallization from EtOAc gives the title compound: m.p.: 203-204° C.; TLC(EtOAc/EtOH/NH3conc. 90:10:1): Rf=0.21.

Aufarbeitung

  1. concentrationthe solution is concentrated in vacuo
  2. dissolutionThe residue is re-dissolved in THF
  3. extractionextracted twice with EtOAc
  4. washThe organic phases are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customChromatography (Combi Flash; EtOAc→EtOAc/EtOH+2% Et3N 4:1) and crystallization from EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-b11b88d8435b4f00859ff49ea7ebce20
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07855215B2

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